Progress in Hematology Recent Progress in Gene Therapy

International Journal of Hematology

, Volume 99, Issue 4, pp 361-371

First online:

Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies

  • Marco L. DavilaAffiliated withLeukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center
  • , Diana C. G. BouhassiraAffiliated withCenter for Cell Engineering, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center
  • , Jae H. ParkAffiliated withLeukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center
  • , Kevin J. CurranAffiliated withDepartment of Pediatrics, Memorial Sloan-Kettering Cancer Center
  • , Eric L. SmithAffiliated withLeukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center
  • , Hollie J. PegramAffiliated withLeukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center
  • , Renier BrentjensAffiliated withLeukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center Email author 

Abstract

The genetic modification of autologous T cells with chimeric antigen receptors (CARs) represents a breakthrough for gene engineering as a cancer therapy for hematologic malignancies. By targeting the CD19 antigen, we have demonstrated robust and rapid anti-leukemia activity in patients with heavily pre-treated and chemotherapy-refractory B cell acute lymphoblastic leukemia (B-ALL). We demonstrated rapid induction of deep molecular remissions in adults, which has been recently confirmed in a case report involving a child with B-ALL. In contrast to the results when treating B-ALL, outcomes have been more modest in patients with chronic lymphocytic leukemia (CLL) or other non-hodgkin’s lymphoma (NHL). We review the clinical trial experience targeting B-ALL and CLL and speculate on the possible reasons for the different outcomes and propose potential optimization to CAR T cell therapy when targeting CLL or other indolent NHL. Lastly, we discuss the pre-clinical development and potential for clinical translation for using CAR T cells against multiple myeloma and acute myeloid leukemia. We highlight the potential risks and benefits by targeting these poor outcome hematologic malignancies.

Keywords

CAR Hematologic malignancies Adoptive T cell therapy